Liquid biopsy on chip: a paradigm shift towards the understanding of cancer metastasis

Abstract

This comprehensive review serves as a guide for developing scalable and robust liquid biopsies on chip for capture, detection, and analysis of circulating tumor cells (CTCs). Liquid biopsy, the detection of biomarkers from body fluids, has proven challenging because of CTC rarity and the heterogeneity of CTCs shed from tumors. The review starts with the underlying biological mechanisms that make liquid biopsy a challenge before moving into an evaluation of current technological progress. Then, a framework for evaluation of the technologies is presented with special attention to throughput, capture rate, and cell viability for analysis. Technologies for CTC capture, detection, and analysis will be evaluated based on these criteria, with a focus on current approaches, limitations and future directions. The paper provides a critical review for microchip developers as well as clinical investigators to build upon the existing progress towards the goal of designing CTC capture, detection, and analysis platforms.

Advances in liquid biopsy on-chip for cancer management: Technologies, biomarkers, and clinical analysis

“…The recognition element is the piece that allows for analyte specificity, and can be immune recognition, size or physical parameter based, or based on electrochemical cues[14], [20]. The choice of recognition element is generally based upon the biomarker analyte desired and the required specificity of the system.…”

“…Liquid biopsy involves gathering information about a disease through a liquid sample rather than a tissue sample[8], [13], [14], [21]–[23]. Typically, cancer is diagnosed through clinical pathology, with a tissue biopsy or imaging to screen or diagnose various types of cancer.…”

“…Before liquid biopsy technologies can be discussed in full detail, it is important to understand the types of biomarkers and their biogenesis in cancer. The main biomarkers that have been studied in liquid biopsy for cancer include circulating tumor cells (CTCs), extracellular vesicles called exosomes, and circulating nucleic acids such as DNA and miRNAs[14], [21]–[23]. These biomarkers are shed off into the bloodstream, urine, saliva, or cerebrospinal fluid from the tumor site and can be detected in the fluid and further analyzed to improve clinical understanding of the patient condition, as shown in Figure 3.…”

“…Thus, there has been a trend towards on-chip technologies that allow for tumor biomarker capture and analysis in a single simple workflow. These technologies hold a lot of promise for patient diagnosis, therapeutics, monitoring, and prognosis in a variety of settings without requiring invasive sample acquisition[14]. …”

Liquid biopsy - emergence of a new era in personalized cancer care

“…A major drawback of EpCAM based platform is the high variation in the gene expression between tumor subtypes and its downregulation during epithelial-tomesenchymal transition (EMT) of cancer cells [124]. Therefore, EpCAM based platforms have provided only modest sensitivity in detecting CTCs [125].…”